Abstract 173P
Background
FS222 is a novel tetravalent bispecific antibody targeting PD-L1 and CD137 that aims to overcome the limitations of current PD-(L)1 and CD137 (4-1BB) monotherapies via a unique mechanism of action that elicits PD-L1-dependent CD137 activation. This has the potential to deliver strong antitumor clinical activity, even in PD-L1 low conditions as seen in preclinical models, with good tolerability.
Methods
FS222 is being evaluated in an open-label, multi-center study in patients with advanced treatment-refractory solid tumors. Part A consists of single patient cohorts in an accelerated dose titration followed by a 3+3 design and pharmacokinetic/pharmacodynamic (PK/PD) expansion cohorts. Patients received FS222 intravenously every 4 weeks until disease progression or unacceptable toxicity. Adverse events and dose-limiting toxicities (DLTs) were primary endpoints. Efficacy (RECIST 1.1), PK, immunogenicity and PD biomarkers were secondary endpoints. Efficacy (iRECIST) and further PD biomarkers were assessed as exploratory endpoints.
Results
As of 20th July, 2022, 33 patients (median age: 58 years) were treated with FS222 at doses of 300 μg (n=1), 1 mg (n=1), 3 mg (n=1), 10 mg (n=1), 30 mg (n=5), 0.75 mg/kg (n=15) and 1 mg/kg (n=9). 24 patients (73%) were checkpoint inhibitor-naïve. Median time on study was 58 days (range 19-359) with 11 ongoing. One patient experienced a DLT of grade-3 febrile neutropenia and one patient experienced grade-3 transaminase elevation without total bilirubin increase, both at 1 mg/kg. Maximum tolerated dose was not reached and dose escalation is ongoing. Pharmacological activity was demonstrated by increased peripheral soluble target receptors and proliferating CD4+ and CD8+ T cells. At 8 weeks, one patient experienced a complete response (CR), 6 had disease stabilization, 14 had progressive disease (RECIST 1.1), 3 discontinued before week 8, and 9 were awaiting their week 8 evaluation. The CR occurred in a non-squamous NSCLC patient who was naïve to PD-(L)1 therapy, dosed at 1 mg/kg. The CR remained persistent 10 months later.
Conclusions
Thus far, FS222 has demonstrated manageable tolerability and early signs of antitumor activity.
Clinical trial identification
NCT04740424.
Legal entity responsible for the study
F-star Therapeutics Inc.
Funding
F-star Therapeutics Inc.
Disclosure
G.A. De Velasco Oria: Financial Interests, Personal, Advisory Board: Pfizer, Astellas, BMS, MSD, Ipsen, Bayer, Eusa P., Merck; Financial Interests, Personal, Invited Speaker: Pfizer, Astellas, BMS, MSD, Roche, Ipsen, Merck; Financial Interests, Institutional, Research Grant: Roche. E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F.Hoffmann-La Roche, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol Mayers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer; Financial Interests, Personal, Full or part-time Employment: START; Non-Financial Interests, Personal, Principal Investigator, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer Beigene BioInvent International AB, BMS, Boehringer, Boheringer, Boston, Celgene, Daichii Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith: Multiple. I. Melero: Financial Interests, Personal, Advisory Board: Gossamer Bio, Highlight Therapeutics, MSD, Alligator Bioscience, Genmab, Numab, NOXXON Pharma AG, BMS, CRISPR Therapeutics, Genentech, AstraZeneca, Boehringer Ingelheim, EMD Serono, Roche, CatalYm GmbH, BioLineRx, Boston Pharma, Janssen, Hookipa Pharma, HotSpot Therapeutics, Inc., ImmuneSensor Therapeutics, Inc., Monopteros Therapeutics; Financial Interests, Personal, Other, Consultant: Pharma Mar; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, BMS, Genmab, Alligator. A. Cervantes: Financial Interests, Institutional, Advisory Board: MerckSerono, Amgen, Roche, Transgene, AnHeart Therapeutics; Financial Interests, Institutional, Invited Speaker: Amgen, Roche, Merck Serono, Foundation Medicine; Financial Interests, Personal, Other, Associate Editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editor: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal Investigator: Actuate Therapeutic, Amgen, Astellas Pharma, Beigene, Bayer, AstraZeneca, BMS, Amcure, FibroGen, Lilly, Genentech, MedImmune, Merck Serono, Novartis, Natera, MSD, Servier, Sierra Oncology, Adaptimmune, Takeda; Non-Financial Interests, Personal, Other, General and Scientific Director: INCLIVA Biomedical Research Institute. D. Jones: Financial Interests, Personal, Stocks/Shares: F-star Therapeutics Inc. M.A. Lakins: Financial Interests, Personal, Stocks/Shares: F-star Therapeutics Inc. L. Kayitalire: Financial Interests, Personal, Stocks/Shares: F-star Therapeutics Incs. All other authors have declared no conflicts of interest.